H-benzo[f]chromen-3-one [2AHBC] in binary solvent mixtures of acetonitrileand 1,4-dioxane at room temperature and explores the fluorophore asan antimicrobial material. Our findings throw light on the key performanceof organic molecules in the medicinal and pharmaceutical fields, whichare considered as the most leading drives in therapeutic applications.In view of that, fluorescence quenching data have been interpretedby various quenching models. This demonstrates that the sphere ofaction holds very well in the present work and also confirms the presenceof static quenching reactions. Additionally, the fluorophore was firstinvestigated for druglike activity with the help of in silico tools, and then it was investigated for antimicrobial activity throughbioinformatics tools, which has shown promising insights.The present studyharnesses fluorescence quenching between a nonfluorescentaniline and fluorophore 2-acetyl-3 The fluorescence quenching study helps in understandingthe dynamic changes of proteins in complex macromolecular systemsto navigate microbial cell growth, etc.7 The main reason for fluorescence quenching is various molecularinteractions such as energy relocation, molecular reorganization,collisional quenching, and ground-state complex formation.8 However, quenching mechanisms are also affectedby the type of the quencher and the nature of the fluorophores.9 Fluorescence quenching can be employed to studyprotein folding at the single-molecule level,10 and further is constructive to acquire information about the conformationaland/or dynamic changes of proteins in complex macromolecular systems.11Thefluorescence quenching mechanism has become an imperative spectroscopictool to investigate biophysical and biochemical systems in differentliquid media. It reveals important information about proteins, membranes,and macromolecular assemblies. For fluorescence quenching studies,we generally select quenchers such as carbon tetrachloride, aniline,bromobenzene, various metal ions, and quantum dots. The selectionof quencher for the respective fluorophore mainly depends on the suitabilityof the molecular electronic structure of the quencher with the fluorophore.etc.12 They are the most widely used organic substances in therapeuticapplications as photochemotherapy, antibacterial, anti-inflammatory,antitumor, and anti-HIV therapy agents, central nervous system (CNS)stimulants, and anticoagulants and dyes. A recent study on coumarinshows that coumarin-containing drugs can decrease estrogenic activity,which arises during menopause.14 Over the past few decades,technological improvements in both optics and electronics have greatlyexpanded fluorometric applications, predominantly in analytical fields,as a consequence of the high sensitivity and specificity affordedby the techniques. Using fluorometry in the study and conservationof cultural heritage is a recent development.15 The recent outburst in new fluorescence applications is acceleratingthe rapidity of research and development in basic and applied lifesciences, including genomics, proteomics, bioengineering, medicaldiagnosis, and industrial microbiology. Fluorescence-based techniquesare extensively used to address fundamental and applied questionsin the biological and biomedical sciences. The current use of fluorescence-basedtechnology includes assays for biomolecules, metabolic enzymes, DNAsequencing, research into biomolecule cell signaling dynamics andadaptation, and fluorescence in situ hybridization(FISH) to identify specific DNA and/or RNA sequences in tissues. Recently,molecular methods have been applied to fuse the gene for the greenfluorescent protein (GFP) to other genes, leading to its expressionin living cells. This allows a sophisticated breakdown of gene expressionand cellular location of important structural proteins and enzymes.Extreme selectivity of fluorescent labels that can target specificorganisms opens new avenues to resolve industrially and medicallyrelevant problems in areas such as public health, the safety of foods,and environmental monitoring. Innovative fluorophores, new techniquesincluding spectrally and temporally resolved fluorescence, and purpose-engineeredinstrumentation create niche commercial opportunities and lead towardtangible industrial outcomes. Fluorescence spectroscopy is one ofthe most sensitive and versatile instruments in medical, biological,and biochemical research. Table S1 listssome of its numerous applications.16Coumarins have been the most importantcompounds for photophysicalstudies during the last few decades, as they are exceedingly fluorescentin nature. Coumarin is a plant-derived product that is naturally availablein different plants such as cassia cinnamon, tonka beans, strawberries,apricots, black currents, 19 Coumarins haveshown significant growth in the use of fluorescence in biologicalsciences, especially in biochemistry and biophysics, along with environmentalmonitoring, clinical chemistry, DNA sequencing, and genetic analysisby fluorescence in situ hybridization. Especiallyin molecular biology, fluorescence is used for cell identificationand sorting in flow cytometry and in cellular imaging to reveal thelocalization and movement of intracellular substances by means offluorescence microscopy. Because of the high sensitivity of fluorescencedetection, there is continuing development of medical tests basedon the phenomenon of fluorescence. These tests include widely usedenzyme-linked immunoassays and fluorescence polarization immunoassays.The fluorescence quenching of coumarins provides beneficial informationabout structural and dynamic properties. Studies have shown that effectivelyadding a substituent group to the parent molecule influences and enhancesthe biochemical and pharmacological properties.in silico and antimicrobial studies.Hence, the above insights have enlightened us to undertake a detailedanalysis on the title fluorophore. This present study would help usto find the possible applications of 2AHBC for molecular imaging andbiomedical applications.In the literature, only few articles are focused on fluorescencequenching of coumarin compounds in binary solvent mixtures, ADMET,molecular docking, 22.1H-benzo[f]chromen-3-one [2AHBC] was freshlysynthesized as reported in the literature.20 Aniline is used as a quencher. Acetonitrile (ACN) and 1,4-dioxane(DXN) solvents are selected to prepare binary solvent mixtures. Thesolubility of the solute was checked prior to conducting the experiment.The solvents ACN, DXN, and quencher aniline were procured from S-DFine Chemicals Ltd., India; they were of HPLC grade and used as received.To minimize self-quenching and reabsorption, the concentration ofsolute was kept minimum (1 × 10–6 M) in allof the solvent mixtures. Preparing a fresh solution prior to conductingthe experiment would help in getting good results. The aniline concentrationvaried from low 0.00 M to high 0.01 M in all of the binary mixtures.The fluorescent probe 2-acetyl-32.2The study of spectroscopic properties was carried out in variousconcentrations of ACN + DXN mixture by measuring absorption spectrausing a UV/vis spectrophotometer (model: U-3300) with a wavelengthaccuracy of 0.5 nm and emission spectra using a Hitachi spectrophotometerF-7000 at room temperature. For every measurement, the spectrometerwas calibrated for the baseline. All of the glassware were cleanedwell prior to preparing the solutions. Fluorescence lifetime measurementswere carried out for the 2AHBC molecule with and without a quencherusing a spectrometer . All of the resultsobtained from the experiments can be reproducible within 5% of theexperimental error.2.3Pseudomonas aeruginosa is a facultativepathogen,which has very high medical importance because of its resistant nature. P. aeruginosa is a multi-drug-resistant pathogenbecause of its ubiquitous nature. Intrinsic mechanisms that are responsiblefor the resistance have a great impact on the illness caused.21 A number of therapeutic targets to target P. aeruginosa have already been studied, but it isvery important to select a target that is part of the antibiotic resistancemechanism. Targeting proteins involved in antibiotic resistance notonly helps in reducing resistance but also helps in controlling thegrowth of pathogens.21 To find a suitabletarget, the complete genome of P. aeruginosa was downloaded with assembly idGCF_000006765.1 from NCBI Genome.The downloaded genome was submitted to the ARTS tool for the predictionof essential (core) genes and resistant gene models.222.4Adsorption, distribution, metabolism excretion,and toxicity analysis(ADMET) is one of the valuable processes present in the discoverypipeline of drugs. The main aim of ADMET studies is to find the physiochemicalproperties of the compound, which are a very important part of compounddesign and optimization. Oral absorption, receptor toxicity, clearance,and brain dispersion are significant features to be observed in ADMETstudies.24 The structure of 2-acetyl-3H-benzo[f]chromen-3-one was obtained from the PubChemdatabase (Pubchem id: 748172),25 and thestructure was optimized using Open Babel26 with minimization steps of 5000; the weighted rotor search methodwas employed to generate 50 conformations for the compound, and minimizationwas carried out using the steepest descent method.27 In the current study, Erythronate-4-phosphate dehydrogenasewas chosen as the target based on the ARTS prediction. The crystalstructure of the protein was downloaded from the PDB database28 and a reference-based docking study was carriedout using Autodock vinatool.29 The gridbox was generated with the specification of 3.5 Ao areas around thebound cocrystallized ligand.30Molecular docking is performed to calculate the bindingaffinity and the best possible mode of the ligand in a complex withprotein.2.5In vitro antibacterialcapability of the synthesized compound,2-acetyl-3H-benzo[f]chromen-3-one,was evaluated by the agar well diffusion technique according to themethod published previously by Yaraguppi et al.30 The pathogens were obtained from the Microbial Type CultureCollection and Gene Bank (MTCC), Chandigarh, and the National Collectionof Industrial Microorganisms (NCIM), Pune. The antibacterial effectwas assessed against Gram-positive bacteria like Micrococcusluteus (NCIM 2871), Bacillus cereus (NCIM 2217), Bacillus subtilis (NCIM2718), and Staphylococcus aureus (MTCC737). Also, it has been tested against Gram-negative pathogens suchas Escherichia coli (MTCC 443), Salmonella typhimurium (MTCC 98), P. aeruginosa (MTCC 2297), and Klebsiellapneumoniae (MTCC 109). The pathogenic cultures (24h broth) were spread-plated on the nutrient agar plates. Wells werecreated on the inoculated plates with a sterile cork borer for loadingthe compound. 2-Acetyl-3H-benzo[f]chromen-3-one  preparedin dimethyl sulfoxide (DMSO) was filled in the agar wells and allowedfor diffusion. The compound-loaded plates were incubated for 24 hat 35 ± 2 °C. DMSO and gentamicin were used as negativeand positive controls, respectively. The zone of inhibition (mm) wasrecorded. The in vitro antifungal property was examinedby employing the agar disk diffusion method following the method reportedby Bagewadi et al.31 The compound wastested against a selected pathogen, Candida albicans, which is our lab isolate. The fungal pathogen was grown in potatodextrose broth (24 h) and inoculated on potato dextrose agar plates.The compound was loaded on Whatman filter paper no. 1 disks (6 mm)and kept on the agar plates. The inoculated cultures were incubatedfor 48 h at 30 ± 2 °C. The inhibition zone (mm) was measured.Positive control was clotrimazole.The 2.632 using microdilution technique. The synthesized compoundstock (5 mg mL–1) was diluted (using DMSO as diluent)to achieve a concentration between 5 and 0.625 mg mL–1. The bacterial pathogen P. aeruginosa was inoculated in nutrient broth and agitated with the respectiveconcentrations of the compound for 24 h incubation (35 ± 2 °C).The turbidity was assessed by recording OD at 660 nm.MIC is known as the maximum dilution of the compoundthat exhibits the inhibition of microbial growth. The MIC was executedas per the method illustrated by Bagewadi et al.33.1H-benzo[f]chromen-3-one [2AHBC] is presentedin The molecular structure of 2-acetyl-3i.e., 100% ACN, to a low polar solvent, i.e., 100% DXN. This is attributed to the dipole–dipoleinteraction between the solute and the solvent molecules in the excitedstate than in the ground state.Typical absorption and emission spectra of 2AHBC were recordedwith and without aniline at room temperature and are shown in 340 = 1.10 ns.However, as seen in 3.235 respectively, and are shown in KSV = kqτ0 called the Stern–Volmerconstant, kq is the bimolecular quenchingrate constant, and τ0 represents the lifetime ofthe excited solute molecule in the absence of quencher [Q].Thebehavior of the solute molecule under the influence of binary solventmixtures on the fluorescence quenching mechanism has been studiedwith the help of S-V relations. With the help of 36 The presence of static quenching may be thereason for the presence of static quenching. By comparing 37 in ACN + DXN solventmixtures. It signifies that the presence of static quenching is eitherdue to the sphere of action model or the formation of the ground-statecomplex.40In the present case, the S-V plot in the steady state shows theconcave upward curve in all ACN + DXN solvent mixtures.W represents the partiallyquenched particles, 1 – W represents the unquenchedparticles, I0 is the intensity of thesolute without a quencher molecule, and I is theintensity of the solute with a quencher molecule. The S-V quenchingconstant (KSV) and a portion of the quenchedparticles (W) can be easily determined from 41 However, the kinetic distance (r) and volume ofthe static quenching constant (V) are evaluated bythe relation According to the modified Stern–Volmerequation, S-V plotswere constructed in the steady state and are shown in Figure 3.3kg representsthe association constant.The nonlinearbehavior of the S-V plot can be analyzed by incorporating eq 42 As we have observed aslight bathochromic shift in absorption spectra and considerable bathochromicshift in emission spectra, we applied the ground-state complex modelusing spectral data. But, unfortunately, we have obtained all kg values as imaginary. Hence, we can suggestthat the ground-state complex model does not hold well for the presentmolecule in all ACN + DXN solvent mixtures.18This model can also be applied whenthere is any considerable change in the absorption or emission spectrumof the solute.3.4RS) and quencher (RQ). The obtained results were correlated withthe literature.43 It is observed that the calculated values of encounter distance(R) are almost double the kinetic distance (r) in all of the binary solvent mixtures. This demonstratesthat the present work obeys the sphere of action model44 and hence confirms the presence of static quenchingreactions. However, static effects can also be evident from diffusion-limitedreactions.45 Further, the concave upwardcurve from the linearity in the S-V plot signifies the simultaneousoccurrence of static and dynamic quenching.46The bimolecularparameters and quenching rate constants were determined by a modifiedS-V plot for 2AHBC. 3.549KSV0 = 4πN′ RDτ0ka/(4πN′ RD + ka). Using slopes and interceptofthe linear plot of KSV–1 against [Q]1/3, the value of KSV0 at [Q] = 0 and diffusioncoefficient D were determined. KSV0 can alsobe written asR′) is evaluated using 49 provided ka > kd, i.e., for R′ < R, and kq > 4πN′R′ D for R′ > R. evaluated from 51 However, according to Zeng andJoshi46 et al., quenching reactions are said tobe diffusion-limited only when R′ is largerthan R andthe mutual diffusion coefficient (D) were determinedand are presented in Da and Db and R′ and R in all of the ACN + DXNsolvent mixtures. This is due to the deviations in the values of theadjustable parameter “a” in the Stokes–Einsteinrelation and the approximated values of the atomic volume in the Edward′sempirical relation.53 A similar discrepancywas observed in other studies.60 Hence, we can conclude that thefinite sink approximation model helped us only to extract D and R′ values.Using KSV against the dielectric constant(ε) for 2AHBC. It was observed that with an increase in thedielectric constant of the solvent mixture, there was an increasein KSV, which shows the improved reactionrate and charge transfer nature. As we continue to increase the polarnature of the solvent, the dielectric constant increases, which inturn stabilizes the reacting species. The fluorescence quenching willbe more pronounced for polar solvents with increasing dielectric constants,which might be due to the effect of the hydrogen bond on a radiationlessdeactivation process. This indicates an elevated charge transfer natureof the exciplex in the ACN + DXN solvent mixtures. Similar resultswere reported in other literature studies.59Furthermore, theeffect of the dielectric constant of the solventmixtures on the quenching constant of 2AHBC was studied. kd) against the inverse viscosity of different binary mixtures. Asseen in kd, andquenching rate parameter, kq, increasewith a decrease in viscosity. Hence, we can conclude that quenchingis controlled by material diffusion. As shown in KSV) was correlatedwith the viscosity of the binary solvent mixture. For the presentmolecule, an inverse dependency of viscosity of solvent mixture on KSV was observed.51 The fluorescence quenching has no major impact or a less pronouncedimpact on the viscosity of solvents. This is attributed to the mechanismssuch as single–triplet conversion, charge transfer complex,and chemical reactions that might play a role.3.6P. aeruginosa genome for the possible antibiotic-resistanttargets was carried out using ARTS (Antibiotic-Resistant Target SeekerV2). The analyzed genome showed that the genome of P. aeruginosa consists of a total of 5681 genes,out of which 584 genes are core genes or the essential genes, 13 genesare part of biosynthetic pathway gene clusters, and 63 genes are antibiotic-resistantmodels. Erythronate-4-phosphate dehydrogenase is one of the enzymesthat are an essential protein in the lifecycle of P.aeruginosa and is also part of the antibiotic-resistantmodel. The three-dimensional (3D) crystallized structure of erythronate-4-phosphatedehydrogenase was obtained from the PDB (Protein Data Bank (PDB) id: 2O4C).61The analysis of the 3.6.1H-benzo[f]chromen-3-one are presented in Table S2. ADMET analysis of the compound 2AHBCwas carried out, and it was seen that the compound passed Lipinski’srule of drug-likeness. It was also predicted that the compound hashigh GI absorption and is also BBB permeate. The best fit was selectedbased on the binding affinity score and based on the interactionswith the important residues of erythronate-4-phosphate dehydrogenase.The target protein structure was further cleaned by removing the watersusing Autodock tools, and the cocrystallized ligand of NAD+ was furtherremoved for the molecular docking. The binding space of the cocrystallizedwas analyzed, and the key residues were identified. A total of 103water molecules were removed from the structure.62Molecular dockingwas carried out on erythronate-4-phosphate dehydrogenase with compound2AHBC (Pubchem id: 748172) to find the best possible mode of binding.Details of ADMET properties of the compound 2-acetyl-3x = 27.37, y = 85.45, and z = 2.32, and the size of the grid box for the docking was 25 pointsfor x, y, and z coordinates. The docking of erythronate-4-phosphate dehydrogenasewith the optimized structure of 2AHBC was carried out with exhaustivenessof 100 (high accuracy), and the binding affinity was determined tobe −7.9 kcal mol–1. A comprehensive analysisof the complex was done, and the involvement of key amino acid residuesin the active site is tabulated in The grid box for the docking was considered basedon the coordinates of the cocrystallized ligand. The coordinates were 3.7In vitro antimicrobial attributes of 2AHBC arepresentedin P. Aeruginosa (23.3± 0.9 mm) (Gram-negative bacteria) and B. subtilis (19.5 ± 0.8 mm) (Gram-positive bacteria). In vitro antifungal activity of 2AHBC against C. albicans was also promising, with a 16.7 ± 1.3 mm zone of inhibitionbased on the analysis of the agar disk diffusion method. No effectwith DMSO (negative control) and inhibitory effect with standard gentamicin(positive control) were observed. Evaluation of the MIC of the compoundagainst P. aeruginosa was carried outconsidering the highest inhibitory effect shown on the pathogen. P. aeruginosa was found to be susceptible, exhibitingsignificant inhibition with a MIC of 2.5 mg mL–1 -3H-benzo[f]chromen-3-ones with antibacterialpotential against E. coli and S. aureus. An application of antimicrobial polyurethanecoating using 2--3H-benzo[f]chromen-3-one (a coumarin thiazole derivative) possessingantimicrobial potential has been reported by El-Wahab et al.64 Raj et al.65 synthesizedseveral compounds and studied the antimicrobial effect and MIC againstseveral bacterial and fungal pathogens, but none of the compoundscould inhibit the growth of P. aeruginosa, and interestingly, we report the inhibition of P.aeruginosa by our synthesized compound. Studies showedthat the electron-withdrawing groups usually exhibit the antifungalactivity of the compounds against C. albicans and Candida tropicalis. The electron-releasinggroup may possibly promote the antibacterial effect against Gram-positivepathogens, and electron-withdrawing groups may trigger antibacterialeffects against both Gram-positive and Gram-negative microbial strains65 as reported for newly synthesized 2H-benzo[h] chromene derivatives as a group of antibacterialadjuvants that exhibit effective biological properties. However, notmuch literature is available on the antimicrobial properties of thecompound 2-acetyl-3H-benzo[f]chromen-3-one.Each data value represents the mean±SD value of triplicate experimentsand is significant at p < 0.05. mg mL–1 14. Bacte4kq wasfound to be greater than 4πN′R′D. Hence, quenching reactionswere found to be diffusion-limited. There was a nonlinear dependencyon the dielectric constant of the binary solvent mixture, and KSV suggests high charge transfer of the exciplexin the binary solvent mixture and an inverse dependency of viscosityof solvent mixture on KSV. The fluorescencequenching is more efficient in polar solvents, and in them, quenchingdecreases as the viscosity of the medium increases. This is attributedto the mechanisms such as single–triplet conversion, chargetransfer complex, and chemical reactions that might play a role. Wealso expect fluorescence quenching to find its application in studyingother biological processes, such as RNA folding or conformationalchanges of enzymes during functioning. In view of this, the fluorophorewas first applied for druglike activity, and then it was checked forantimicrobial activity through bioinformatics tools, which showedpositive results. Docking studies were performed for its antimicrobialactivity against a facultative pathogen P. aeruginosa, as it is multi-drug-resistant. We have selected erythronate-4-phosphatedehydrogenase, which is part of the antibiotic resistance mechanism.After positive in silico studies, in vitro studieswere carried out with selected pathogens to prove their antimicrobialactivity, and the results were encouraging, with a higher zone ofclearance for P. aeruginosa comparedto other pathogens in the study. These considerations can stronglyindicate that fluorescence quenching mechanisms are useful and extensivelyappropriate to obtain enriched information about the structure anddynamics of biologically important macromolecular systems.Fluorescence quenching of 2AHBCin solvent mixtures of ACN + DXNwas analyzed. The Stern–Volmer plot showed a concave upwardcurvature in the presence of quenchers. The studied system obeys thesphere of action static quenching model and confirms the presenceof static quenching. For 2AHBC,


Doping is a great strategy for tuning the characteristics of graphene-based nanomaterials. Phosphorous has a higher electronegativity as compared to carbon, whereas boron can induce p-type conductivity in graphene. This review provides insight into the different synthesis routes of phosphorous- and boron-doped graphene along with their applications in supercapacitors, lithium- ions batteries, and cells such as solar and fuel cells. The two major approaches for the synthesis, viz. direct and post-treatment methods, are discussed in detail. The former synthetic strategies include ball milling and chemical vapor discharge approaches, whereas self-assembly, thermal annealing, arc-discharge, wet chemical, and electrochemical erosion are representative post-treatment methods. The latter techniques keep the original graphene structure via more surface doping than substitutional doping. As a result, it is possible to preserve the features of the graphene while offering a straightforward handling technique that is more stable and controllable than direct techniques. This review also explains the latest progress in the prospective uses of graphene doped with phosphorous and boron for electronic devices, i.e., fuel and solar cells, supercapacitors, and batteries. Their novel energy-related applications will continue to be a promising area of study. In the last few decades, rapid industrialisation has resulted in a high demand for energy, which is coupled with the depletion of natural resources . The sciThe rapid progress of research on doped graphene analogues can be seen in the high number of publications   and the s-orbital, out of the three p-orbitals, are used to produce covalent bonds with nearby carbon atoms, whilst the pz orbital is employed to produce a filled π bonding molecular orbital and a vacant π* anti-bonding molecular orbital ,492 hybrThe doping of graphene with heteroatoms offers redox active sites, which enhance the capacity of the probes and electrodes. Previously, a review article covering the detailed discussion on environmental application of phosphorous- and boron-doped graphene nanosheets was published . In addiP-GNS can be synthesised either by direct or post-treatment methods. In direct methods, a carbon source such as benzene, toluene, alginate, and glucose, etc., is reacted with a phosphorous source, viz. phosphorous trichloride, triphenylphosphine, phosphoric acid, or phosphorous pentaoxide, to yield P-GNS. In the latter methods, previously synthesised GO is reacted with a phosphorous source such as tri-n-octylphosphine, tetradecylphosphonic, tri-n-butylphosphine acid, phosphoric acid, triphenylphosphine, polyphosphoric acid, or triphenylphosphine, to produce P-GNS. The synthesis methods, sources, and the applications of P-GNS are summarized in 3) and benzene (C6H6) in the temperature range of 800–1050 °C in a chamber was used to synthesise P-GNS (Direct pyrolysis of phosphorous trichloride (PClse P-GNS  74]. Th. Th3) an4 molecules and substitutional doping within the graphitic matrix can cause phosphorous atoms to interact with the graphitic lattice below the material’s surface. Measurements using an X-ray photoelectron spectroscopy (XPS) technique showed that phosphorous was bonded to carbon with two bonding configurations, P–C or P–P. However, the P–O bonds were also observed near the material’s surface. At a low phosphorous content, phosphorous existed in two different bonding configurations where the P–O bonds were observed at high phosphorus contents, and P–C species were difficult to detect because their signals overlapped.Both free, stable P−1 argon flow rate. The BET surface areas of the P-GNS and the non-phosphorous material were similar.Liu et al.  synthesiP-GNS was synthesised by the pyrolysis of phosphoric acid as the phosphorous-containing source and alginate as the carbon-containing source at 900 °C under inert atmosphere . Graphen2O5) was used as the phosphorous precursor and glucose was used as the carbon source. The phosphorous source displayed a temperature-dependent transformation as shown in the following reaction  wasD/IG, was 1.25, which was greater than the undoped graphene (0.92). The G band is related to the C–C vibrational mode, while the D band, the defect activated band, is related to sp2 hybridized carbon nanomaterials. The ID/IG ratio gives indication about the defect densities. The amount of phosphorous in P-GNS was 1.78 at.%. The insertion of phosphorous induced structural disorders into the graphitic lattice. Due to phosphorous’ excellent electron-donating qualities, this finally improved the electron delocalization. As a result, the conductivity and charge transfer were improved.The amount of phosphorous varied from 1.0 to 6.0 g for 2.0 g of glucose. With an increase in phosphorous content, the mesoporosity was observed to rise. The Raman spectra revealed that the defect ratio of the D to G band, i.e., I2. The two characteristic Raman bands of reduced GO were observed at 1350 and 1590 cm−1, respectively. The D band displayed a red shift in P-GNS and there was a decrease in intensity of ID/IG. The XPS spectra of P-GNS displayed peaks at 134.4 eV and 133.5 eV due to P–O and P–C bonding, respectively [The thermal decomposition method involves chemical decomposition of a substance in the presence of heat. The reaction is endothermic in nature as heat is required to break the covalent bonds. P-GNS can be prepared by this approach using phosphoric acid, triphenylphosphine, tri-n-octylphosphine, tetradecylphosphonic, and tri-n-butylphosphine acid as doping agents. Yuan et al. used phosphoric acid to dope reduced GO. During annealing, the oxy groups were removed with the release of CO and COectively . VariousSong and coworkers studied the formation of P-GNS using the thermal decomposition method of three different phosphorous-containing surfactants  at two different temperatures, 800 and 900 °C. The mixed surfactant systems led to more efficient doping as compared to a single surfactant due to an increase in d-spacing , which resulted in more penetration of the phosphorous atoms into this spacing .Non-volatile and thermally stable 1-butyl-3-methylimidazolium hexafluorophosphate was used by Li et al. for in situ phosphorous doping of graphene nanosheets. The amount of phosphorous in P-GNS was 1.16 at.%. During the annealing process, he P-GNS .2 under argon atmosphere. The fraction of graphitic and elemental phosphorous in P-GNS prepared in the absence of H2 was higher than the same synthesised in the presence of H2. The sample was purified and any remaining high-oxidation state phosphorous species in P-GNS was eliminated by the reductive conditions formed by H2 at 1000 °C, as evidenced by the atomic percentage of P being 79% vs. 69% of the entire signal. The XPS studies showed different peaks at 129.6 eV, 131.0 eV, and 132.5 eV, attributed to elemental phosphorous, graphitic phosphorous, and oxidized graphitic phosphorous, respectively [MacIntosh et al. synthesised P-GNS from GO using triphenylphosphine as a phosphorous source at 1000 °C with or without the presence of Hectively .3PO4 as an electrolyte and phosphorous source. Anhydrous H3PO4 phosphoric acid facilitated the exfoliation of the graphite layers. Upon dilution, H3PO4 dissociated into H+ and PO43− ions, which passed through the graphite layers and cleaved to form a P-GNS. The HR-TEM micrographs revealed wrinkled and folded graphene sheets. The XPS analysis of P-GNS showed 0.68 at.% phosphorus, confirming the P-doping in GNS. Moreover, the electrochemical activity of P-GNS was enhanced as compared to GNS [The electrochemical erosion method is the most effective way to create doped GNS in the presence of direct current and graphitic electrodes. Thirmual et al. prepared P-GNS using Hd to GNS .Different boron precursors such as triisopropyl borate, triethylborane, phenylboronic acid, diborane, boron powder, boron oxide, benzene-1, 4-diboronic acid, boric acid, and orthoboric acid can be used for the synthesis of B-GNS. Different synthesis methods along with the various sources used and the applications are summarized in 3)3, acted as a boron-containing source that decomposed at a high temperature and reacted with the atoms of carbon to make B–C bonding configurations as follows:In the CVD methodology, the growth substrate is reacted with volatile compounds leading to the formation of the desired materials under inert conditions . High-qu3 to sp2 conversion of the C–C bond. Cattelan et al. also synthesised B-GNS using diborane, boron-containing source and methane, and carbon-containing precursor, using polycrystalline copper foil as a growth substrate [2BO and CBO2 was also considered. Three- to five-layered graphene was synthesised using this method at 950 °C directly on copper substrates in the presence of boron powder as the boron source and ethanol as the carbon precursor with a boron content of 0.5 at.% [2 V−1 s−1 carrier mobility at room temperature [2/Ar with a 4.3 at.% of B [3) bonding configuration where carbon atoms were replaced by boron atoms was common, but a boron silane (BC4) configuration occurred due to excess edge sites and defects [The DFT calculations showed that the incorporated elemental form of boron accelerated the spubstrate . There w0.5 at.% . B-GNS h0.5 at.% . The XPS0.5 at.% . The Ramperature . Boric at.% of B . Similar defects .The CVD method has an advantage that large area B-GNS are allowed to be synthesised easily . However2O3 as the boron source [4) and boron tribromide (BBr3) in the presence of potassium resulted in the generation of B-GNS at 150–210 °C in 10 min. The amount of boron was about 2.56 at.% as determined by XPS analysis [Self-assembly is a bottom-up approach where the components of an unorganised system assemble themselves to form a larger functional unit by non-covalent interactions. Selva and coworkers were able to dope reduced GO up to 10 and 20 at.% boron using Bn source . The atoanalysis . This me2H6), and H2. Vapours of B2H6 were produced by the introduction of boron triflouride-diethyl etherate to sodium borohydride in the presence of tetraglyme. The B2H6 vapours were carried to the arc chamber by first passing the H2 at 200 Torr and then He (500 Torr) through the B2H6 generator. In the second approach, boron-packed graphite electrodes were used to conduct the arc discharge for the synthesis of B-GNS in the presence of H2 (200 Torr) and He (500 Torr). The XPS analysis showed that B-GNS synthesised using the second approach contained an increased amount of boron (3.1 at.%) as compared to the first approach (1.2 at.%) [An electrical breakdown of an inert gas causes an arc-discharge, which results in a prolonged electrical discharge. Panchakarla used this method in two different ways to synthesise B-GNS. In the first approach, B-GNS were synthesised employing the arc-discharge of graphite electrodes in the flow of helium (He), diborane (B.2 at.%) . Palnitk.2 at.%) . The pre2O3) was ultrasonically mixed with an aqueous solution of GO; and in the second step, thermal annealing of the mixture was carried out at four different temperatures  for simultaneous reduction and doping. The schematic representation is shown in 3 and BC2O, respectively. At 1000 °C, the peak at 190.8 eV became more predominant because of the reduction of oxygeneous moieties and the formation of more B–C bonds. High temperature favoured the formation of the B–C bonds rather than the B–O bonds. The maximum boron concentration in BT-rGO was found to be (6.04 ± 1.44) at.% at 1000 °C [Thermal annealing is a process of altering the surface morphology of materials and the key factor determining the bonding configuration is temperature. Yeom et al. synthesised thermally reduced boron-doped graphene oxide (BT-rGO) in a two-step reaction. Firstly, a boron precursor (B 1000 °C .3 and Ar (1:4 v/v) with a 250 mL min−1 of total flow rate for 2 h. The XPS peaks were obtained corresponding to BC3 and BC2O nanodomains  and is useful for growing single crystals from a solution in an autoclave at a high temperature and pressure. Thirumal et al. used a two-step thermal approach to synthesise B-GNS. Firstly, GO was thermally reduced at 500 °C (T-GNS), and in the second step, T-GNS was treated with boric acid in a Teflon- lined autoclave to produce boron-doped graphene (HB-GNS) .3BO3) as the boron source [2O3). The boron oxide then diffused into the lattice of graphene and the carbon atoms were substituted by boron as follows [B-GNS was also obtained via a one-step hydrothermal method using boric acid  showed two bands. The D band peak position at 1351 cmd of GOF . This meFew reports are available in which the vacuum activation method is used for the synthesis of boron-doped graphene nanoribbons. Xing et al. used boric acid as a boron-containing precursor to synthesise boron-doped graphene nanoribbons. Graphene maintained its decreased micrometer-sized structure after vacuum reduction and ultrasonic processing, but after doping with boron, the large-scaled graphene sheets were cut into nanoribbons. The substitutional boron doping caused a macro-residual stress, which promoted the growth of nanoribbons. The size of the graphene sheets was successfully reduced with boron doping and the conductivity of B-GNS was improved .P-GNS has been studied for its applications in electronic devices ,82, enerFuel cells are used to convert the energy from a chemical nature to an electrical nature. Hydrogen gas is fed into the anodic compartment where it is oxidised and the oxygen gas is fed into the cathodic compartment where it is reduced. The ORR is the rate-determining step that occurs in the cathodic compartment . ORR can3OH) in electrolyte inhibits the ORR at the platinum surface. This can be avoided by metal-free electrocatalyst such as P-GNS. Phosphorous atoms increase the absorption and cleavage of the oxygen– oxygen bond due to the charge polarization of the heteroatom and carbon bond. Qiao and coworkers reported that dual-doped graphene (PN-GNS) synthesised by pyrolysis of GO (as the carbon source) and diammonium hydrogen phosphate (as the nitrogen and phosphorous source) acted as a better electrocatalyst as compared to single-doped and undoped graphene [The poisons such as carbon monoxide (CO) and methanol (CHgraphene . The syngraphene .0.8Sr0.2MnO3). The introduction of perovskite to undoped graphene increased the number of electrons (n) moved from anode to cathode electrode 2.7 to 3.6 at −0.5 V, but it did not alter the current density. This problem was overcome by fabricating perovskite with dual-doped graphene. Here the n value increased to 3.8 at −0.5 V. This may be due to acceleration or conductivity effects provided by perovskite. The kinetic analysis showed that the direct four-electron pathway was favoured [The ORR activity of dual-doped graphene can be further improved by their fabrication with inexpensive perovskite such as  showed excellent electrocatalytic activity, which was five to six times higher than P-GNS and two times higher than NS-GNS . A similShewanella oneidensis bacteria, displaying a comparable catalytic current density to Pt/C [Nitrogen-, iron-, sulphur-, and phosphorous-doped graphene was synthesised using the direct pyrolysis of  to Pt/C . The pre to Pt/C . The enh to Pt/C . The BPNLithium-ion batteries are important energy-producing and storage devices. These are rechargeable batteries, which contain lithium solution as an electrolyte. The importance of lithium-ion batteries in energy-related devices nowadays can be understood from the Nobel Prize given in 2019 to three scientists, Stanley Whittingham, John Goodenough, and Akira Yoshino, for their innovation in the synthesis of lithium-ion batteries. The use of these lightweight, rechargeable, and powerful lithium-ion batteries from electronic gadgets to electric vehicles have revolutionized our lives. The negative electrode of a conventional lithium-ion cell is composed of carbon-based materials, while the positive electrode is a metal oxide. During charging, ions move from anode to cathode and the reverse happens during discharging. Due to its low affinity for lithium atoms and the tendency of deposited lithium atoms to cluster on the graphene surface, pure graphene is not a good choice for lithium storage . Moreove−1), with nearly no loss across 80 cycles, indicating that P-GNS-based electrodes possess a good longevity [−1 at a current density of 1000 mA g−1. Due to low abundance and uneven global distribution of lithium ions, the increasing demand of Li-ion batteries can hardly be meet.Zhang’s group used P-GNS in lithium-ion batteries as an anode material for the first time. They also compared the results with undoped graphene and found that P-GNS acted as a superb electrode because of various topological defects introduced on its surface during the doping process. This led to a randomized carbon lattice that improved the lithium insertion characteristics. P-GNS has a considerably larger reversible discharge and charge capacity than undoped graphene  (474 mA h g−1 after 50 cycles at 50 mA g−1 and 160 mA h g−1 after 600 cycles at 2000 mA g−1). This might occur as a result of the dopants’ high inter-layer spacing, which aided the insertion and extraction of potassium ions [P-GNS is also a viable option for anodes in sodium-ion batteries . Na-ion ium ions .Supercapacitors have high capacitance values as compared to conventional capacitors because they link the gap between rechargeable batteries and electrolytic capacitors. They are also known as gold caps, ultracapacitors, or super caps. Supercapacitors come in a variety of forms, including hybrid capacitors, electrochemical pseudocapacitors, and electrostatic double-layer capacitors. The first type of supercapacitors use carbon materials for electrode preparation, and charge separation is achieved using the Helmholtz double layer at the junction of the electrolyte and the surface of a conductive electrode. In electrochemical pseudocapacitors, conducting polymers and metal oxide electrodes are used and charge separation is achieved by Faradaic electron charge transfer with electrosorption, intercalation, and redox reactions. In the third type, hybrid capacitors are a combination of both electrodes; one that stores the charge faradaically and the other stores the charge electrostatically.Due to graphene’s enormous surface area and large electric double-layer capacitance, it has recently been employed as an electrode in supercapacitors . However−1, a high specific capacitance of 367 Fg−1, and a high energy density of 59 Wh kg−1. After many hundreds of cycles, there was no discernible loss in any particular capacitance. Thirumal et al. [−1 at a current density of 0.5 Ag−1. Thus, the different approaches affect the capacitance values because different defects are created by the different methods. DFT relates the enhanced specific capacitance of P-GNS with structural changes in the lattice. DFT calculations were used by Song et al. [Graphene doped with phosphorous exhibited improved capacitive performance in aqueous electrolyte due to higher pseudocapacitance and a strong conducting network in the graphene structure. A supercapacitor was created by Karthika et al. , utilisil et al.  also syng et al.  to ident−1 at a current density of 1 Ag−1 [−1 at 1 Ag−1), which was six times higher than bare polyaniline. Moreover, this value further increased with an increase in current density from 1 to 15 Ag−1 [Polyaniline–graphene-based electrodes exhibited high specific capacitance of 480 Fgf 1 Ag−1 . This va 15 Ag−1 .−1 at 0.05 Ag−1 current density was present in PN-GNS. P-GNS is a superior supercapacitor electrode than a broad potential window of 1.6 V in an aqueous electrolyte because it contains functional groups that include phosphorus [Because of the synergistic effects of the heteroatom dopants, co-doping of heteroatoms has been seen as a potential way to improve the energy storage performance of graphene-based materials. Excellent specific capacitance of 183 Fgosphorus .The applications of B-GNS are discussed in different subsections, viz. solar cells, sensors, supercapacitors, lithium-ion batteries, fuel cells, and photocatalysts. The properties of the materials are briefly discussed in next subsections.The substituted boron atoms in the graphene lattice acted as active sites for adsorption of oxygen and speeding up oxygen–oxygen bond breaking. Molina-Garcia et al.  observed3 and graphitic N were the main active sites among various boron doping or/and nitrogen configurations. Mazanek et al. [Wu et al.  carried k et al.  also synk et al. .−1) and a low onset potential (−0.10 V), BNP-GNS demonstrated excellent electrocatalytic activity [With a high current density (55 A cmactivity . Due to activity .2), and transparent conducting layer (fluorine tin oxide) [2-based solar cell with an open current voltage of 0.53 V, and a short current density of 18.8 mA cm−2 was developed by Li et al. [The solar cell is an electrical device that changes sunlight or artificial light into electrical energy through the photovoltaic effect and thus it is also known as the photovoltaic cell. The absorption of light energy, which produces excitons or electron–hole pairs, is one of the three fundamental characteristics needed for a solar cell to function. The separation of charge carriers of different types is the second step, and the independent extraction of those carriers to an external circuit is the third step. Dye-sensitized, organic, quantum dot, perovskite, and perovskite solar cells are examples of common solar cells. The four layers of a solar cell are the interface layer , hole transport layer -9,9′,-spiro bi fluorene), electron transport layer (TiOn oxide) . The pown oxide) . A B-GNSi et al.  under oni et al. ,131. The2-adorned B-GNS for use as a lithium-ion battery anode material. In comparison to bare SnO2 and B-GNS, they discovered that the synthesised hybrid had the largest reversible capacity of 744 mAh g−1 at a current density of 100 mAh g−1. An improved lithium interaction resulted from the SnO2, a spacer within the GNS, increasing the likelihood of lithium intercalation and alloying against re-stacking of the 2D planes. Due to the wrinkled graphene network and homogenous dispersion of tiny SnO2 nanoparticles (NPs), a rise in reversible capacity was seen with increasing boron content in B-GNS [Due to their low memory loss, high energy density, and low self-discharge rate, rechargeable lithium-ion batteries are extensively employed in portable electronic devices . Using ain B-GNS .−1 at 50 mA g−1). This anode showed increased cycle stability and reversible capacity of 540 mAh g−1 at 100 mAh g−1 after 100 consecutive cycles. The presence of defect sites and heteroatoms in the presence of boron and Ag NPs was attributed to these outstanding electrochemical performances. Tian et al. [−1 at 0.1 C after 100 cycles. The excellent high rate of performance was attributed to the B-strong rGO’s electrical conductivity. The composite cathode’s electric conductivity was enhanced and the shuttle effect was delayed by boron doping on rGO. Due to the co-dopants’ synergistic effects, BN-GNS produced by the hydrothermal process performed better than single-doped graphene. For the objective of preserving active material during the cycle and enhancing the carbon’s wettability in the organic electrolyte, borax and nitrogen dopants had significant binding opportunities with polysulfide species [Silver (Ag) NPs embedded on B-rGO served as the anode material in a nanocomposite that was synthesised by Bindumandhavan et al. . Due to n et al.  have als species . The nex species .−1 and low migration barrier of 0.07 eV. This may be due to the substrate being doped with boron, which causes it to become electron-deficient and causes a sizable charge transfer from potassium to the substrate. Due to the inhibition of dendritic development and prevention of potassium atom clustering, there is good cycling stability [Potassium-ion batteries are gaining popularity as lithium-ion battery substitutes due to the abundant availability of potassium in the Earth’s crust. B-GNS has the potential to be used as an anode material for potassium-ion batteries due to its high specific capacity of 546 mAh gtability ,137.−1, which was three times higher than reduced GO (135 Fg−1). A supercapacitor’s specific capacitance typically depends on the electrode’s BET surface area and electrical conductivity, both of which decrease as the annealing temperature rises. On the other hand, boron-doped GO lowered the electrical conductivity and BET surface area increased as the annealing temperature rose from 300 to 1000 °C. At a higher temperature (1000 °C), the doping of boron heteroatoms may create defect-like small pores in the graphene nanosheet’s plane that prevents the growth of graphitic structure [Supercapacitors based on doped graphene electrodes showed higher interfacial capacitance as compared to undoped ones. Some researchers reported that the presence of dopant on the graphitic lattice might lead to electrochemical reduction–oxidation reactions on the surface, which would ultimately enhance the capacitance of the material. The specific capacitance of boron-doped reduced GO was 448 Fgtructure .2SO4 at various current densities (1 Ag−1 to 4 Ag−1). The curves of charge–discharge were triangular in shape  measurements on thermally reduced graphene and B-GNS in 0.5 M Hin shape a, and CVin shape b, which ectively c,d, whicNumerous publications also examined the effects of co-doping graphene with two or more heteroatoms. Chen et al. produced BN-GNS with atoms ranging from 0.6% to 2.1% (B) and 1.74 to 2.56% (N). In order to get a satisfactory performance in electrochemical energy storage, dopants were simultaneously introduced, creating a synergistic effect between boron and nitrogen . The finHeteroatom doping is one of the best techniques for altering the properties of graphene. Depending on the type of heteroatom dopant such as boron, nitrogen, phosphorous, sulphur, and fluorine, and doping configurations, heteroatom-doped graphene nanomaterials can be used for a spectrum of applications.In this review, we have discussed direct and post-treatment methods for the synthesis of P-GNS and B-GNS. As compared to B-GNS, research on P-GNS is still in its infancy and the comparative evaluation of heteroatom doping on the structural, textural, and morphological properties is still unexplained. Various characterisation tools, viz. XPS, TEM, SEM, Raman coupled with DFT calculations, have been used to study the structural properties of doped graphene-based nanomaterials. The starting dopant material, precursors, temperature, reaction time, and other factors all affect the characteristics of the obtained materials. However, due to the heterogeneity of the doped graphene, conflicting results are reported and the current understanding of the characteristics of heteroatom-doped graphene is still insufficient. The innovative uses of doped graphene materials for energy conversion, energy storage, and gas storage have been addressed. Because of their fast electron transport and three-dimensional porous structure, materials based on doped graphene perform better in energy-related devices. Because of the additional possibilities offered by heteroatom doping, graphene research will continue to flourish. Despite the positive advancements made in the field of doped graphene-based materials, there are still numerous obstacles that need to be overcome, viz. the limited number of publications demonstrating their applications towards the environmental field and biological toxicity. These issues need to be critically considered to extend their practical applications and for their large-scale applications.


Previous studies using contemporary cardiac troponin (cTn) assays have shown conflicting results in predictability of mortality and major adverse cardiovascular events (MACEs) in hemodialysis patients. We aimed to evaluate the prognostic values of high-sensitivity cTnT (hs-cTnT) and hs-cTnI for long-term mortality and MACEs in asymptomatic chronic hemodialysis patients. 198 asymptomatic patients undergoing regular hemodialysis (age 62.4 ± 14.8 years) were enrolled. Pre-dialysis hs-cTnT and hs-cTnI levels were measured. The study outcomes were long-term all-cause mortality and MACEs. Median values of hs-cTnT and hs-cTnI were 61.1 ng/L (IQR 36.6–102.0) and 18.4 ng/L (IQR 9.5–36.6), respectively. During a median follow-up of 13.5 months, 30 (15.1%) patients developed MACEs, and 20 (10.1%) patients died. The patients in highest quartile of hs-cTnT level (≥ 102 ng/L) had increased risk of long-term mortality . However, hs-cTnI levels above highest quartile (≥ 36 ng/L) was not significantly associated with increased risk of all-cause mortality. Nevertheless, elevated level of hs-cTnT and hs-cTnI was associated with increased risk of MACEs. We demonstrated that higher level of hs-cTnT, but not hs-cTnI, was associated with increased risk of long-term mortality. Nevertheless, higher level of hs-cTnT and hs-cTnI both were associated with greater risk of long-term MACEs. Early recognition of patients undergoing hemodialysis with heightened mortality risk is essential for the early intervention and attentive therapy. Multiple biomarkers have been explored to be used as a predictor of long-term adverse outcome in this population2. Several investigators have shown that asymptomatic patients with end-stage renal disease (ESRD) have chronically elevated levels of cardiac troponin (cTn)6. Recent studies have demonstrated that nearly all of patients with regular dialysis had a raised level of high-senstivity cTnT (hs-cTnT), while around one-third of patients had an increased level of high sensitivity cTnI (hs-cTnI)9. The dissimilar findings between cTnT and cTnI may be attributable to the distinctions in cellular distribution, biochemical, genetic, and kinetic features11. With this regard, it has been suggested that hs-cTnI may be more favorable in the diagnostic use of patients with suspected acute coronary syndrome6. However, in terms of prognostic values between cTnT and cTnI in patients with ESRD, the data are still conflicting13. In addition, conventional cardiac troponin assay used in those studies may have drawback of limited sensitivity and specificity as compared to high-sensitivity assay. Based on the revised definition of myocardial infarction with strict recommendations on test precision, the high sensitivity assay of cardiac troponin T and I has gained popularity in its use. As a result, we aim to evaluate and compare the prognostic value of the hs-cTnT and hs-cTnI assay for long-term mortality and major adverse cardiovascular events (MACEs) in asymptomatic patients receiving regular hemodialysis.It is well-established that the patients with chronic hemodialysis had a markedly higher rate of cardiovascular death and all-cause death than the general populationIn this prospective observational cohort study, ESRD patients, aged more than 18 years, who had undergone regular hemodialysis for more than 3 months at the hemodialysis unit at Chiang Mai University hospital were enrolled. All of the participants who had an acute myocardial infarction, heart failure, or pulmonary embolism within the past 6 months; recent major or traumatic surgery within the last 4 weeks; and recent coronary and/or valvular surgery within the last 6 months were excluded from this study. A total of 200 patients with chronic hemodialysis were screened for eligibility. Two patients were excluded due to the occurrence of acute coronary syndrome in one patient and heart failure requiring hospitalization in one patient within the past 6 months. As a result, there were 198 asymptomatic patients with chronic hemodialysis enrolled in this study during a period of September 2020 to January 2021. Patients who underwent a kidney transplant or who were lost to follow-up were censored on the day of the transplant as well as the day of their final visit. This study was approved by the institutional research board of Faculty of Medicine, Chiang Mai University . Informed consent and all procedure followed the Declaration of Helsinki and ethical standards of the responsible committee on human experimentation.15. Therefore, we chose to obtain the blood sample of pre-dialysis hs-cTnT and hs-cTnI levels during the long dialytic period. The hs-cTnT was analyzed by electroluminescence immunoassay using Cobas e801 (Roche Diagnostics) and hs-cTnI with the ARCHITECT i2000SR Diagnostic System (Abbott). The limit of detection was 3 ng/L for hs-cTnT and 3.2 ng/L for hs-cTnI, and the coefficients of variation below 10% were 13 ng/L and 4.7 ng/L for hs-cTnT and hs-cTnI. The cutoff at the 99th percentile was 14 ng/L for hs-cTnT and 26.2 ng/L for hs-cTnI.Clinical data were acquired at the time of study entry, including age, gender, cardiovascular risk factors, medication, comorbidity, blood chemistry, and hemodialysis data . The pre-dialysis hs-cTnT and hs-cTnI levels were measured in all subjects (single measurement). Several studies have revealed that cardiovascular events are more frequently after a long interdialytic interval than after a short interdialytic interval during hemodialysis sessionsAll participants were followed for the first occurrence of all-cause mortality and MACEs until September 2021. The primary endpoint was the prognostic values of hs-cTnT and hs-cTnI on all-cause mortality, with the secondary endpoint being the prognosis for MACEs. MACEs were defined as a composite outcome of nonfatal myocardial infarction, heart failure hospitalization, and death from any cause.https://www.ibm.com/products/spss-statistics) was used for statistical analysis and STATA version 16.2  was used for graphic creation.Continuous variables were expressed as means and standard deviations when normally distributed, or medians and interquartile ranges when not normally distributed. The comparison across the different groups was performed using the Mann–Whitney U test or the Student t-test. Categorical variables were presented as frequency (%) and compared between groups using Fisher's exact test. A Kaplan–Meier time-to-event curve with a log-rank test was performed to compare the outcome by cardiac troponin quartile. The Cox proportional hazards regression model was used to assess the association between cardiac troponin levels and the risk of adverse cardiovascular events. The prognostic value of hs-cTnT and hs-cTnI on all-cause mortality and MACEs was determined as a hazard ratio (HR) and 95% confidence interval (CI). Statistical significance was defined as a P-value of less than 0.05. The statistical software package SPSS version 23  patients who had level of hs-cTnI above this gender-specific cutoff point.A total of 198 asymptomatic patients with chronic hemodialysis were enrolled in this study. The median follow-up durations were 13.5 months, one patient lost to follow up and one received a kidney transplant. Table Among 198 patients with regular dialysis, the first occurrence of MACEs was reported in 30 patients (15.2%), including nonfatal myocardial infarction in 7 patients, heart failure hospitalization in 7 patients, and death from any cause in 16 patients. Among 30 patients who developed MACEs, 2 patients with nonfatal myocardial infarction and 2 patients with heart failure hospitalization subsequently died in separate events. As a result, a total of 20 (10.1%) patients died during follow-up, in which cardiovascular death occurred in 9 patients (4.5%).The non-survivors were significantly older than the survivors . Atrial fibrillation was non-significantly more prevalent in non-survivors , leading to the greater use of oral anticoagulants in non-survivors compared to survivors . The higher use of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) was also evident in non-survivor group . The presence of other co-morbidities did not differ between non-survivors and survivors. The significantly lower levels of hemoglobin and serum albumin were observed in non-survivors. Interestingly, non-survivors had significantly greater hs-cTnT levels compared to survivors , while hs-cTnI levels were not statistically different between two groups (p = 0.105)  and hs-cTnI (≥ 36 ng/L) and those with values below the highest quartile. The univariable and multivariable Cox regression analysis of hs-cTnT and hs-cTnI on long-term all-cause mortality were shown in Table A cut-off level of hs-cTnT ≥ 102 ng/L provided a sensitivity of 50%, a specificity of 78.1%, a positive predictive value of 20.4% and a negative predictive value of 93.0% to predict long-term mortality. Apart from the level of hs-cTnT, age was also another independent predictor of long-term mortality.According to the secondary outcome, patients with hs-cTnT level in the highest quartile was associated with a greater risk of MACEs  compared to those in the lower quartile.  and free cTnT. On the contrary, cTnI was more hydrophobic and was detected dominantly in the binary complex (I-C) form, with lesser extents of the ternary (T-I-C) complex. Degradation of the complex led to more rapidly clearance of the protein23. The Vitros ES assay manufactured by Ortho Clinical Diagnostics was used in that study. Other studies from Artunc and colleagues have also shown that hs-cTnI was associated with long-term mortality. The troponin I Ultra assay on a Siemens ADVIA Centaur system was used in their studies24. On the other hands, our study along with others which demonstrated the lack of predictive power of hs-cTnI and adverse outcomes used hs-cTnI assay manufactured by Abbott Diagnostics8. With this regard, the diversity of predictive power of hs-cTnI among studies may be resulted from the use of different hs-cTnI assay.Nevertheless, some studies have reported the significant association of hs-cTnI and long-term adverse outcomes. Gaiki and colleagues determined the prognostic value of hs-cTnI in asymptomatic patients with hemodialysis. At a 2-year follow-up, they discovered that using a hs-cTnI was predictive of cardiac eventsOur study confirmed that elevated level of hs-cTnT can be used as a prognostic marker for long-term mortality in patients with regular hemodialysis. The optimal cutoff level of hs-cTnT for predicting the long-term mortality is unknown. We proposed the cutoff hs-cTnT level of 102 ng/L to predict long-term mortality with a sensitivity of 50%, a specificity of 78.1%, a positive predictive value of 20.4% and a negative predictive value of 93.0%.6. Another small study demonstrated that the majority of patients with asymptomatic hemodialysis had relatively constant troponin values after 3 consecutive monthly measurements. Nevertheless, 20% of them had fluctuating troponin values over a 3-month period25. Whether the serial measurement of hs-cTn is a better predictor on long-term outcome than single measurement merits further studies.Our study has a number of limitations. First, our study cohort was recruited from a single dialysis center and our sample size was relatively small. As a result, the generalizability of our findings is limited. Second, we did not include patients with chronic peritoneal dialysis. Therefore, our findings could not be applied in these populations. Third, since cardiac troponin levels were measured only once, it was difficult to show how changes in biomarkers affected the clinical outcome of patients. Fourth, other biomarkers that may have predicted the outcome such as C-reactive protein were not assessed in our studied population. Fifth, the constant effect of a predictor on the outcomes is crucial. Previous study from our group showed that the levels of pre-dialysis hs-cTnI and T did not differ between short interdialytic and long interdialytic intervalsWe demonstrated that elevated hs-cTnT level, but not hs-cTnI, was associated with a higher risk of long-term mortality. Nevertheless, higher level of hs-cTnT and hs-cTnI both were associated with greater risk of long-term MACEs in patients with chronic hemodialysis.


The optimal salvage pelvic treatment for nodal recurrences in prostate cancer is not yet clearly defined. We aimed to compare outcomes of salvage involved-field radiation therapy (s-IFRT) and salvage extended-field radiation therapy (s-EFRT) for positron emission tomography/computed tomography–positive nodal-recurrent prostate cancer and to analyze patterns of progressions after salvage nodal radiation therapy.18F-fluorocholine or 68Ga prostate-specific membrane antigen ligand positron emission tomography/computed tomography–positive nodal-recurrent prostate cancer and treated with s-IFRT or s-EFRT were retrospectively selected. Time to biochemical failure, time to palliative androgen deprivation therapy (ADT), and distant metastasis–free survival were analyzed.Patients with P = .010). The 3-year biochemical failure–free rate was 70.2%  with s-IFRT and 73.9%  with s-EFRT (P = .657). The 3-year distant metastasis–free survival was 74.1%  with s-IFRT and 82.0%  with s-EFRT (P = .338).Between 2009 and 2019, 86 patients were treated with salvage nodal radiation therapy: 38 with s-IFRT and 48 with s-EFRT. After a median follow-up of 41.9 months (5.4-122.1 months), 47 patients presented a further relapse: 31 after s-IFRT and 16 after s-EFRT, with only 1 in-field relapse. The median time to palliative ADT was 24.8 months  in the s-IFRT group and not yet reached  in the s-EFRT group (s-EFRT and s-IFRT for positron emission tomography–positive nodal-recurrent prostate cancer provide excellent local control. Time to palliative ADT was longer following s-EFRT than following s-IFRT. They have better sensitivity and specificity than conventional imaging and make it possible to identify recurrence sites with accuracy at an earlier stage.,Despite the improvement of therapeutic strategies in the management of localized prostate cancer in recent years, 20% to 50% of patients present biochemical failure (BF).Moreover, as some patients will inevitably progress after individualized salvage treatment, we need better knowledge of the course of the disease in this population in order to properly select patients and to propose the most appropriate therapeutic strategy.The objective of this study was two-fold. First, we assessed and compared the feasibility and the efficacy of salvage nodal involved-field radiation therapy (s-IFRT) and salvage nodal extended-field radiation therapy (s-EFRT) in patients with FCH or PSMA PET-positive nodal recurrence from prostate cancer. Second, we analyzed the patterns of failure after salvage nodal radiation therapy in this same population.After institutional review board approval, we retrospectively identified patients with nodal recurrence after local curative therapy for prostate cancer, detected with FCH or PSMA PET/CT and treated with salvage radiation therapy with curative intent in our institution.,FCH and PSMA PET/CT were performed as described previously.An abdominopelvic planning CT scan with 2.5-mm slice thickness was performed starting 5 cm above the diaphragm and ending 2 cm below the ischial tuberosities. Contrast agent was injected in the absence of contraindications. Patients were immobilized in the supine position in a custom blue bag device .Organs at risk were the rectum in toto, the bladder in toto and the bowel loops  and the kidneys.For s-EFRT, a prophylactic CTV including the whole pelvis was delineated as defined by the Radiation Therapy Oncology Group consensus atlas. In patients with PET-positive LN in the common iliac region or lower para-aortic region, this CTV was extended up to the L2/L3 space.3 of any part of the gastrointestinal (GI) tract had to be ≤30 Gy with a maximum of 36 Gy. For LA LN treated with SBRT, the maximum absorbed doses to the kidneys and spinal cord had to be <12 Gy and <18 Gy, respectively. Treatment was prescribed to the periphery of the PTV (80% of the dose covering 100% of the PTV) and dose distributions were normalized to the isocenter.For s-IFRT, GTV was defined as any PET-positive LN delineated after fusion between the planning CT and the CT images from PET/CT. Each CTV was equal to the GTV. A 5-mm margin around the GTV was applied to obtain each PTV. Three-dimensional radiation therapy or intensity modulated radiation therapy were used with the same dose constraints as described for s-EFRT. For stereotactic body radiation therapy (SBRT), the absorbed dose to 0.5 cmThe choice of irradiation was determined according to the previous treatments, the characteristics of the patient, and the practices of the physician.Irradiation was performed on either a TrueBeam, Trilogy, or Novalis linear accelerator equipped with a 120-leaf collimator  depending on the technique used. A cone beam CT scan was performed before each fraction for all patients over the entire course of the radiation therapy to set up patients and verify targets; all shifts were corrected with no minimal action level. In each treatment group, all techniques of radiation therapy were included, and the dose prescription was decided at the discretion of the physician.Treatment characteristics are summarized in ,Follow-up was performed as described previously.Median follow-up times were calculated using the reverse Kaplan-Meier method.In this analysis, a BF was defined using the Phoenix definition.Time to biochemical failure (TTF) was defined as the time between the PET/CT diagnosing the nodal relapse before salvage nodal radiation therapy and the BF. Time to palliative ADT was defined as the time between the PET/CT diagnosing the nodal relapse before salvage nodal radiation therapy and the initiation of palliative life-long ADT. Distant metastasis–free survival (DMFS) was defined as the time between the PET/CT diagnosing the nodal relapse before salvage nodal radiation therapy and distant metastatic progression  or death.The outcomes were determined by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) for univariate and multivariate analyses were estimated using a Cox's proportional hazards regression model with a backward procedure.2 test for categorical variables and the Student t or Mann-Whitney test for quantitative variables .The s-IFRT and s-EFRT groups were compared using the Fisher or χStatistical analyses were performed using SAS 9.4 software .Between January 2009 and April 2019, 86 patients with BF after primary local therapy for prostate cancer had FCH PET/CT or PSMA PET/CT, on which only nodal relapses were diagnosed (82 using FCH PET/CT and 4 using PSMA PET/CT).Patients’ characteristics at diagnosis and at the time of first PET-positive nodal relapses are summarized in At the time of primary disease, 89% of patients were initially treated with exclusive or postoperative radiation therapy in the s-IFRT group and 66% in the s-EFRT group. Twenty-one percent and 12.5% had pelvic irradiation in the s-IFRT group and the s-EFRT group, respectively.P = .019). In the s-IFRT population, almost 87% of patients had only 1 or 2 positive LN compared with >60% in the s-EFRT group. The topography of involved LN was comparable in the 2 populations, more than a quarter of patients had an extra-pelvic nodal recurrence. Eighty-four percent of patients in the s-IFRT group were treated with SBRT. The median dose per fraction to the PET-positive LN was 7.5Gy. Almost 96% of patients in the s-EFRT group were treated with intensity modulated radiation therapy/volumetric modulated arc therapy techniques including 31% with a simultaneous integrated boost. The median prophylactic total dose to the pelvis was 45 Gy and the median total dose to the PET-positive LN was 60 Gy in the s-EFRT group. Twenty-nine patients in the s-EFRT group and 3 in the s-IFRT group received concomitant/adjuvant ADT.Forty-eight patients were treated with s-EFRT and 38 with s-IFRT. There was a significantly higher number of PET-positive LN in the s-EFRT group than in the s-IFRT group . In the s-IFRT and s-EFRT populations, the median follow-up was 63.2 months (6.2-122.1 months) and 33.8 months (5.4-93.2 months), respectively.P = .657). TTF in both groups is presented in Overall, 35 patients had a BF after nodal salvage radiation therapy, 20 in the s-IFRT group (52.6%) and 15 in the s-EFRT group (31.3%). For the whole population, the median TTF was 60 months , and the 3-year BF-free rate was 72.3% . In the s-IFRT and in the s-EFRT populations, the median TTF was 63.2 months  and 58.5 months , respectively, and the 3-year BF-free rate was 70.2%  and 73.9% , respectively (P = .004) and >2 PET-positive LN at the time of failure  in multivariate analysis.Univariate and multivariate analyses are reported in P = .010). Time to palliative ADT following both treatments is presented in Palliative ADT was introduced after nodal salvage radiation therapy in 35 patients. The median time to palliative ADT for the whole population was 41.9 months , the 3-year palliative ADT-free rate was 60.7% . In the s-IFRT and s-EFRT groups, the median time to palliative ADT was 24.8 months  and not yet reached , respectively, and the 3-year palliative ADT-free rate was 46.3%  and 73.8 , respectively (P = .002). Patients treated with s-EFRT were less likely to start palliative ADT . Univariate and multivariate analyses are detailed in The only predictive factor for the initiation of palliative ADT was PSA >3 ng/mL at the time of nodal failure . DMFS of both treatment groups is shown in At last follow-up, 26 patients had distant progression: 17 in the s-IFRT group and 9 in the s-EFRT group. For the whole population, the median DMFS was 82.4 months  and the 3-year DMFS was 78.3% . In the s-IFRT and s-EFRT populations, the median DMFS was 82.4 months  and not yet reached , respectively, and the 3-year DMFS was 74.1%  and 82.0% , respectively (P = .001) and PSA >3 ng/mL at the time of nodal failure  in multivariate analysis. Univariate and multivariate analyses are detailed in Predictive factors for distant metastasis were >2 PET-positive LN . Seven were oligometastatic and all were out of field of nodal salvage radiation therapy. There were 5 pelvic and/or LA nodal and distant metastatic recurrences: 4 in the s-IFRT group and 1 in the s-EFRT group. Location according to the previous irradiation field was not evaluated because all patients had a diffuse supra diaphragmatic and bone metastatic progression. There were 2 local pelvic and/or LA nodal and distant metastatic recurrence: 1 in the s-IFRT group and 1 in the s-EFRT group. Both patients also presented diffuse supra diaphragmatic and bone metastatic progression.The distribution of clinical second relapses are presented in At the second relapse, 9 patients were treated with new salvage radiation therapy (with or without concomitant ADT). One of these patients received a third salvage radiation therapy after new nodal failure.The emergence of FCH and thereafter PSMA PET/CT has made it possible to detect relapse sites in prostate cancer earlier and led to an evolution in therapeutic strategies in recent years. Different local salvage treatments, also named metastasis-directed therapies (MDT), were assessed to provide local control and to delay palliative ADT.P = .11). Tolerance was good in the MDT group with no grade ≥2 toxicity observed, and quality of life was similar in both groups.A randomized phase 2 trial compared the time to the start of palliative ADT following surveillance or MDT (with surgery or SBRT) for PET-positive nodal and/or distant oligorecurrent prostate cancers. The study showed longer ADT-free survival with MDT than with surveillance .P = .009).Ost et al also showed a good tolerance of salvage SBRT for FCH PET-positive nodal oligorecurrences with similar PFS,,For BF in prostate cancer, the addition of 6 to 24 months of ADT to postoperative radiation therapy compared with radiation therapy alone for microscopic residual disease led to benefits in PFS and overall survival.In terms of patterns of failure after salvage nodal radiation therapy, we found an excellent local control and a trend towards a shift in locations. For almost 64% of pelvic LN relapses treated with salvage radiation therapy, the disease progressed to extra-pelvic LN or became metastatic, and almost 64% of extra-pelvic LN relapsed with bone metastases.PSMA PET/CT performed following BF of prostate cancer showed better detection of relapses with low PSA values. Currently, very few data concerning MDT guided specifically with PSMA PET/CT are available. No interpretation could be given in our study; there were only 4 nodal relapses diagnosed with PSMA PET/CT, and 1 of these presented diffuse progression. In a retrospective study that assessed patients exclusively treated with PSMA PET/CT-guided radiation therapy for recurrent oligometastatic prostate cancer, 59% of oligorecurrences were LN and were treated with an extended irradiation field. The authors showed that salvage radiation therapy for PSMA PET/CT-positive oligometastases resulted in effective local control with prolonged biochemical PFS . They also reported a shift in new progressions towards distant LN and skeletal metastases.So far, most published studies on MDT, including those discussed here, have been small, retrospective studies with heterogeneous populations, and have included distant and nodal recurrences. As a result, they cannot be used to establish the optimal management for nodal only oligorecurrent prostate cancers.Our study showed the feasibility of s-IFRT and s-EFRT for PET-positive nodal-recurrent prostate cancer with excellent local control. Time to the initiation of palliative ADT was longer following S-EFRT than following s-IFRT.


R-CHOP with or without radiotherapy is the standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). To prevent overtreatment, we assessed whether four cycles of CHOP plus six applications of rituximab was adequate with negative interim PET/CT and the role of consolidation radiotherapy specifically for patients with Waldeyer’s ring DLBCL. One hundred and twenty-nine patients with limited-stage DLBCL were enrolled in this open-label, nonrandomized, single-arm, phase 2 clinical trial (NCT01804127).All patients were initially treated with 4 cycles of R-CHOP and underwent interim PET/CT. Patients with negative PET/CT (Deauville scores 1–2) received 2 additional cycles of rituximab monotherapy, unless they had any risk factors . Otherwise, patients received another 2 cycles of R-CHOP. Patients with partial response on interim PET/CT received another 4 cycles of R-CHOP. No radiotherapy was conducted in Waldeyer’s ring DLBCL patients with negative PET/CT. The primary endpoint was 3-year progression-free survival (PFS). Overall survival (OS) in this study was compared with those from a historical study (NCT 00854568159).P < 0.05). A trend of inferior outcome was observed in patients with positive interim PET/CT in terms of 3-year PFS  and 3-year OS . There were no PFS or OS differences found between patients treated with 4R-CHOP+2R and those treated with 6R-CHOP from a historical control study. Patients with Waldeyer’s ring DLBCL and negative interim PET/CT achieved a 3-year PFS of 87.2% and a 3-year OS of 89.7%.One hundred fifteen interim PET/CT scans (89.1%) were negative after 4 cycles of R-CHOP. An elevated lactate dehydrogenase level was significantly associated with positive interim PET/CT (Our results suggested that for interim PET/CT-negative patients without risk factors, the extra 2 cycles of CHOP might be omitted, and radiotherapy might also be omitted in patients with Waldeyer’s ring DLBCL without compromising the efficacy. These results need to be confirmed in a randomized study.clinicaltrials.gov, NCT 01804127. Date of first registration: 05/03/2013. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma and accounts for approximately 40% of non-Hodgkin lymphoma cases worldwide , 2.The CHOP  regimen has been the standard chemotherapy regimen for the treatment of DLBCL . In receTo achieve a better response, there have been many efforts to intensify the treatment of R-CHOP, including shortening the interval of therapy and increasing the number of cycles in the early stages. However, two studies in France and the United Kingdom suggested that shortening the interval (R-CHOP14 regimen) failed to have additional benefit based on the conventional R-CHOP21 regimen .Previous studies on elderly patients usually used 8 cycles of rituximab, but the number of cycles of chemotherapy is inconsistent from study to study. There were 8 cycles in the GELA LNH-98.5 study and 6 cycles in the RICOVER-60 study. The latter found that with the combination of rituximab, 8 cycles of chemotherapy even tended to decrease survival –6. For ySince then, an increasing number of studies have focused on de-escalation therapy without compromising efficacy. To prevent overtreatment, the DSHNHL FLYER study enrolled young, very low-risk stage I/II B-cell non-Hodgkin lymphoma patients. They found that 4 cycles of CHOP plus 6 applications of rituximab was noninferior to 6 cycles of R-CHOP .18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is a new type of nuclear medicine assessment that is currently recommended for the response assessment of Hodgkin and non-Hodgkin lymphomas [ymphomas . In receymphomas –16. In tymphomas , 16. TheCurrently, an interim PET/CT-guided therapeutic approach is being actively explored in limited-stage DLBCL. However, few published data are available at present. The Canadian trial requested an interim PET/CT scan after 3 cycles of R-CHOP. For those who obtained negative results, just one more cycle was added . OtherwiDespite its high cost, PET/CT has been gradually recognized as an essential baseline and end-of-treatment assessment in China since the 2010s. Emerging studies on interim PET/CT are mostly conducted in developed countries. Since the interval of R-CHOP therapy had been fixed (R-CHOP21 regimen), to keep up with global standardization and individualized treatment, we are committed to carrying out de-escalation treatment trials to explore the number of cycles of chemotherapy.The standard treatment of Waldeyer’s ring DLBCL with limited stage remains controversial. Li et al.  conducteTherefore, we conducted an open-label, nonrandomized, single-arm, phase 2 clinical trial using response-adapted therapy for limited-stage DLBCL based on interim PET/CT. We assessed whether four cycles of CHOP plus six applications of rituximab was adequate with negative interim PET/CT and the role of consolidation radiotherapy, especially for patients with Waldeyer’s ring DLBCL, to prevent overtreatment.Patients aged between 18 and 80 years with histologically confirmed DLBCL were eligible for inclusion in the study. Patients with limited stage were required to have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of no more than 2 and evidence of adequate organ function. Prior treatment was not allowed. Patients with primary or secondary central nervous system involvement, a known history of other malignant tumours, a known history of HIV or HBV-DNA copies higher than the test value were excluded.All patients underwent baseline PET/CT within two weeks before the commencement of therapy and had positive and measurable lesions on PET/CT. Then, they were initially treated with 4 cycles of R-CHOP . R-CHOP was administered every 3 weeks.An interim PET/CT scan was performed after 4 cycles of R-CHOP on Cycle 4 Day 18 to Day 20 if patients had not progressed after 2 cycles. The Lugano criteria (Cheson 2014)  were useThe primary endpoint was 3-year progression-free survival (PFS), and the secondary endpoints included 3-year OS and objective response rate (ORR). PFS was defined as the interval between the initiation of R-CHOP treatment and disease progression or death from any cause. OS was calculated from the date of the initiation of R-CHOP treatment to the date of death from any cause or the last follow-up.n = 128) treated with 6 cycles of R-CHOP in our centre between March 2009 and December 2012 (NCT 00854568159) [The PFS and OS of negative interim PET/CT patients in this study (treated with 4R-CHOP+2R) were compared with those from a historic group of patients .Categorical variables are expressed as frequencies. The chi-square test was applied to detect differences between groups. PFS and OS were calculated using Kaplan-Meier analysis, with differences between groups compared using the log-rank test, and a difference with ClinicalTrials.gov . All patients provided written informed consent.The study was approved by the institutional review board of Fudan University Shanghai Cancer Center. The trial was registered with From December 2012 to September 2015, a total of 143 patients were enrolled. Among these patients, 129 with baseline and interim PET/CT scans were analysed to evaluate the efficacy at Fudan University Shanghai Cancer Center, Shanghai, China  and 72 men (55.8%) were included. The median age was 50 years . In the entire cohort, 73 (56.6%) of 129 patients had stage II disease, and 9 (7%) of 129 patients exhibited B symptoms. With regard to risk factors , 59 (45.7%) of 129 patients had extranodal primary lesions, and 1 (0.8%) of 129 patients had a bulk > 7.5 cm on CT. Based on the International Prognostic Index (IPI) score, 126 (97.7%) patients had a low risk of relapse  were reported as negative (Deauville scores 1–2). According to the protocol, 63 (54.8%) of 115 patients with negative interim PET/CT scans and no risk factors were treated with 4R-CHOP+2R. Fifty-two (45.2%) of 115 patients with negative PET/CT scans were treated with 6R-CHOP .n = 129).Among 14 patients with positive PET/CT, 13 had PR, and 1 had stable disease. The ORR was 99.2%. With a median follow-up time of 52.5 months, the 3-year PFS rate was 90.5%, and the 3-year OS rate was 94.5% for the entire cohort (P = 0.24) and 3-year OS . However, the differences were not statistically significant . The rest of the characteristics were balanced between the two groups.The chi-square test was applied to detect differences in baseline clinical characteristics between interim PET/CT-positive and PET/CT-negative patients. An elevated LDH level was significantly associated with positive interim PET/CT  in this study. In NCT 00854568159, there were 128 patients with untreated limited-stage DLBCL without risk factors. There were no significant differences in the baseline demographic and clinical characteristics of the patients between the two groups Table .Table 3PThe planned dose intensity and drug propensity of the first 4 cycles of R-CHOP were the same in the two groups. The only difference was that patients with negative interim PET/CT scans in this study received another 2 cycles of rituximab monotherapy instead of another 2 cycles of R-CHOP.P = 0.67; 3-year OS 93.6% vs. 94.5%, P = 0.67)  in interim PET/CT after 4 cycles of R-CHOP and received 2 cycles of rituximab monotherapy, with a 3-year PFS rate of 87.2% and a 3-year OS rate of 89.7%. Involved field radiation therapy was not used in the negative interim PET/CT group.Recently, the role of interim PET/CT in patients with DLBCL was heavily investigated –24. In tThis was a single-arm study performed to directly answer the question of whether omitting the extra 2 cycles of CHOP would affect efficacy. To minimize the interference of race, region, best of supportive care, etc., we compared the survival data with our historical data of the same period in the same centre. Demographic and clinical characteristics were well balanced between these two cohorts. We found that there were no PFS or OS differences between patients treated with 4R-CHOP+2R and those treated with 6R-CHOP. Reducing the number of chemotherapy cycles has a series of benefits, including avoiding adverse events, cutting economic costs and improving quality of life. Therefore, in the case of similar efficacy, we recommend reducing the number of courses of chemotherapy with the reservation of rituximab. The current study was designed in 2012 as one of earliest studies focusing on interim PET in mainland China. PET-CT scans were not covered by medical insurance. Because the budget for the clinical trial initiated by the investigator was limited and we were not sure about the role of interim PET when we initiated this study ten years ago, we started a preliminary phase 2 clinical trial to observe outcomes according to interim PET guidance. Now, we have confidence to conduct a phase 3, randomized controlled trial based on the current data.Similarly, to reduce the adverse events caused by excessive chemotherapy, the FLYER trial was conducted to assess the efficacy of de-escalation therapy . In the 2. If the subsequent 2 cycles of treatment can be omitted without affecting the efficacy, it will undoubtedly reduce treatment-related toxicity, especially cardiotoxicity. Compared to the FLYER study, we tried to answer the question of whether the number of cycles of CHOP chemotherapy can also be reduced in patients older than 60 years or with increased serum LDH levels. The 3-year PFS of the negative interim PET/CT patients who were older than 60 years or had increased serum LDH levels (n = 22) was 89.1% . The survival data for this subset of patients are similar to the data for all patients. On the other hand, there were four patients who were eligible for the FLYER regimen and had positive interim PET-CT in the current study. These four patients who underwent a total of 8 cycles of R-CHOP had a poor prognosis, with a 3-year PFS of 50% . Although these patients had such favourable clinical prognostic factors, there may be some molecular genetic poor prognostic factors that were not tested. The sample sizes of those special groups were too small for statistical analysis. However, the results of these two patient groups provide a strong argument for establishing a randomized controlled trial.The results of both studies investigating the feasibility of de-escalation therapy suggested that chemotherapy could be reduced without compromising outcomes in some specific DLBCL patients. The enrolled populations of the FLYER study and the current study were not the same. The FLYER study enrolled patients aged 18–60 years with stage I-II disease, normal serum LDH, and ECOG PS 0–1 and without bulky disease (< 7.5 cm). However, patients aged between 18 and 80 years were eligible for the current study. Patients with increased serum LDH were also eligible. Although old age is a poor prognostic factor for DLBCL, the cumulative dose of doxorubicin after 6 cycles reached 300 mg/mP = 0.896), and the 5-year OS rates were 96.7% vs. 94.4% (P = 0.649). That study found that radiotherapy did not improve the treatment outcomes in patients with limited Waldeyer’s ring DLBCL with CR after R-CHOP therapy. Compared with those results, the PFS and OS in this study were slightly lower. However, 66.7% of the patients in the immunochemotherapy plus radiotherapy group received more than 6 cycles of immunochemotherapy. In contrast, at least 2 cycles of chemotherapy were further omitted in our study. We believe that the results of the 3-year PFS rate of 87.2% and the 3-year OS rate of 89.7% are acceptable as avoiding the adverse events of overtreatment with radiotherapy and chemotherapy.The standard treatment of Waldeyer’s ring DLBCL with limited stage remains controversial. Consolidation radiotherapy may prolong survival but can cause many acute or chronic toxicities, such as acute oral mucositis, dental decay, and xerostomia , 26. In P < 0.05). Coinciding with our results, the literature described that elevated LDH levels, bulk and bone marrow involvement and poor performance status lead to more positive interim PET/CT [We tried to find the correlation of interim PET/CT status with baseline demographic and clinical characteristics. An elevated LDH level was significantly associated with positive interim PET/CT (m PET/CT . We failAll factors, including the interim PET/CT status evaluated in the multivariate analysis, are listed in Table The early results from this preliminary small-scale, phase 2 clinical trial indicated the possibility of downgrading treatment with overall planning for efficacy, safety and economy.There are some limitations to this study. First, this study is a single-arm, small-scale, phase 2 trial. There is an urgent need for randomized, large-scale trials to answer the question of whether interim PET/CT-negative patients without risk factors could downgrade treatment by omitting 2 cycles of chemotherapy. Second, some new response criteria, such as delta SUV, may be superior for interim PET/CT in DLBCL –35. In fA trend for inferior outcome was observed in patients with positive interim PET/CT. Our results suggested that for interim PET/CT-negative patients without risk factors, the extra 2 cycles of CHOP might be omitted and radiotherapy might also be omitted in patients with Waldeyer’s ring DLBCL without compromising the efficacy and can avoid the adverse events of overtreatment. These results need to be confirmed in a randomized study.


The detection of food safety and quality is very significant throughout the food supply. Stable dual-emission copper-modified fluorescent carbon dots (Cu-CDs) were successfully synthesized by a simple and environment-friendly hydrothermal, which was used for the real-time detection of pesticide residues in agricultural products. By optimizing the reaction conditions, Cu-CDs showed two emission peaks, with the highest fluorescence intensities at 375 and 450 nm. The structure, chemical composition and optical properties of Cu-CDs were investigated by XRD, TEM and IR. The results showed that thiophanate methyl (TM) could induce fluorescence quenching of Cu-CDs with no other ligands by the electron transfer through π-π stacking. The synchronous response of the dual-emission sensor enhanced the specificity of TM, which showed remarkable anti-interference capability. The fluorescence quenching degree of Cu-CDs had a good linear relationship with the TM concentration; the low detection limit for a pear was 0.75 μM, and for an apple, 0.78 μM. The recoveries in the fruit samples were 79.70–91.15% and 81.20–93.55%, respectively, and the relative standard deviations (RSDs) were less than 4.23% for the pear and less than 3.78% for the apple. Thus, our results indicate the feasibility and reliability of our methods in detecting pesticide residues in agricultural products. The fluorescence emission intensity of Cu-CDs solution was calculated; the detection limit was 0.75 μM, and the limit of quantitation was 2.25 μM. 0/F = 0.99711 + 0.01620 [TM]. The correlation coefficient R2 was 0.996, the detection limit was calculated as 0.78 μM and the limit of quantitation was 2.34 μM, which was compared with other strategies reported in the literature as summarized  to test the applicability and accuracy of the prepared Cu-CDs sensor in actual samples . After aCu-CDs with dual-emission fluorescence characteristics were prepared by introducing transition metal doping for the rapid detection of pesticide residues in food. Under the excitation of a single excitation wave of 290 nm, Cu-CDs showed two obvious fluorescence emission peaks at 375 nm and 450 nm. Our detailed study showed that the introduced transition metal copper could not only enhance the fluorescence intensity of CDs but also provide abundant surface-active sites. A fast and sensitive sensor was designed for the determination of TM residues in agricultural products based on the principle that TM could chelate with the active site on the surface of Cu-CDs and have π-π stacking with its benzene ring, which caused the synchronous fluorescence quenching of Cu-CDs. The fluorescence quenching can be observed immediately. By optimizing the detection conditions, the fluorescence quenching degree of Cu-CDs showed a good linear relationship with TM concentration. In fruit samples, the low detection limits for the pear and apple were 0.75 μM and 0.78 μM, respectively, and the limits of quantitation for the pear and apple were 2.25 μM and 2.34 μM, respectively. Our results show that the product has high sensitivity, which can be verified in the detection of agricultural product samples.